Field of the Invention
The present invention relates to microfluidic devices and systems and, more specifically, to microfluidic devices and systems that include the use of external chips or cartridges that fluidically interface with microfluidic chips having one or more microfluidic channels.
Description of Related Art
Microfluidic chips are being developed for “lab-on-a-chip” devices to perform in-vitro diagnostic testing, including nucleic acid diagnostic assays, such as Polymerase Chain Reaction (“PCR”). The largest growth area for the use of such devices is in the field of molecular biology, where DNA amplification is performed in the sealed channels (“process channels”) of the microfluidic chip. In one type of diagnostic assay that can be performed using such chips, optical detection devices are commonly used to measure the increasing amplicon product over time (Real Time PCR) and/or to perform a thermal melt to identify the presence of a specific genotype (High Resolution Thermal Melt). Exemplary disclosures related to the imaging of a microfluidic chip to measure the fluorescent product can be found in commonly-owned U.S. application Ser. No. 11/505,358 to Hasson et al. entitled “Real-Time PCR in Micro Channels” (U.S. Pat. Pub. 2008-0003588) and U.S. application Ser. No. 11/606,204 to Hasson et al. entitled “Systems and Methods for Monitoring the Amplification and Dissociation Behavior of DNA Molecules” (U.S. Pat. Pub. 2008-0003594), the respective disclosures of which are hereby incorporated by reference.
Conventional microfluidic chips comprise cartridges or cassettes with fluidic networking channels and sample/assay distribution wells formed therein. A typical microfluidic chip may comprise at least one or more microfluidic channels, fluidic connection holes, and reagent/waste wells. Microfluidic channel sizes are typically in the range of 10 to 300 μm, the sizes of fluidic connection holes are from 200 to 1500 μm, and the diameters of reagent/waste wells are typically in the range of 2000 to 5000 μm. Biological (chemical) reactions and assays take place within the microfluidic channels, or process channels, of the chip. A detection window may also be provided on the chip to enable detection of a characteristic of the reaction materials within the microfluidic channels, such as optical detection of reaction material colors. In addition, certain other process steps, such as thermal cycling and thermal melt, occur within the microfluidic process channels. To enable accurate optical detection and precision flow control, manufacturing tolerances of the process channels are quite stringent, and such chips are typically made of materials with superior optical qualities, such as glass, silica quartz, or high quality polymers.
Other functionality in the microfluidic chip includes the input, routing, mixing, and output of reaction materials (e.g., samples and reagents), which may be provided by flow structures that are ancillary to the process channels. Such ancillary fluid structures, (i.e., the “plumbing” of the chip) may be provided by various wells, such as a sample input well associated with each process channel, a waste well (pre and/or post process channel) associated with each process channel, and reagent input wells accessible to some or all process channels, and channels and connecting ports for mixing and routing the material to and from the process channels. Devices such as the Caliper sipper chip uses one or more sipper tubes attached to the microfluidic chip to access fluid samples and reagents held in a separate, free-standing microtiter plate. Such sipper tubes may be used as alternatives to or in combination with input wells formed in the chip itself.
In conventional microfluidic chips, the wells (input and/or waste wells) are connected directly to the fluidic holes coupling the process channels to the well(s). As a consequence, because the wells are much larger than the process channels, the chip capacity (i.e., the number of microfluidic process channels on the microfluidic chip) is limited by the size of the wells rather than that of the process channels. Moreover, channels in this portion of the microfluidic chip (i.e., the ancillary fluid structures) need not be as small and precisely manufactured as the process channels and there is no need for superior optic qualities in this part of the chip. Accordingly, the precision and material quality requirements in this part of the chip need not be as high as in the part of the chip containing the process channels.
FIGS. 1 and 2 depict a standard microfluidic chip assembly 10 having a microfluidic chip 18 having formed therein multiple microfluidic process channels 24 and fluidic connection holes 20, 22 on each end of each of the channels 24. Assuming a left-to-right flow direction through the process channels 24, fluidic connection hole 20 functions as an inlet port and fluidic connection hole 22 functions as an outlet port. Microfluidic chip 18 may be formed from multiple layers, such as upper layer 18a and lower layer 18b. As shown in FIG. 2, such a microfluidic chip 18 may be used with a secondary cartridge 12 that fits over top of the microfluidic chip 18, such that the fluidic connection holes 20, 22 of the microfluidic chip 18 line up directly with fluid input and/or waste collection wells 14, 16 of the secondary cartridge 12. Again, assuming a left-to-right flow direction, well 14 is a fluid input well for receiving fluid (e.g., sample, reagent, or a combination thereof) to be delivered to the inlet port 20, and well 16 is a waste collection well for receiving fluid from the outlet port 22. In this manner, the user can supply quantities of materials to the reagent wells which can then be drawn into the microfluidic chip via methods known in the art such as vacuum pressure, positive pressure, electrokinetics, capillary action and the like. Similarly, materials that have traversed the microfluidic channels can be drawn into the waste wells via the same methods.
Assembly 10 is limited by the size of the microfluidic chip 18 and the spacing of the process channels 24 on the chip in order to allow the direct placement of the wells 14, 16 present on the secondary cartridge 12 directly over the fluidic connection holes 20, 22, respectively, of the microfluidic chip 18. That is, the number and size of wells 14, 16 are constrained by the need to correspond directly to the fluidic connection holes 20, 22 and the process channels 24 of the microfluidic chip 18.
There are several challenges that exist in connection with the development of in-vitro diagnostic microfluidic chips including how to perform multiple sample tests simultaneously and how to access a large number of reagents, primers and assays efficiently to screen for desired tests. Current high throughput systems are located in hospital and clinical laboratories. These systems are often very large (with robotic system, pumps, tubes, and reservoirs) and very expensive to operate in point-of-care testing facilities. The desired goal is to develop an efficient assay delivery system for performing multiple sample tests on a desktop system.
Thus, there exists a desire for methods and apparatus to provide larger volume reagent and waste wells to microfluidic chips, specifically in a manner that allows for an increase in the number of microfluidic channels that can be placed on a chip without being confined by the size of necessary reagent/waste wells.
Accordingly, cost savings and other efficiencies can be achieved by minimizing the size of the microfluidic chip formed from costly materials and requiring precise manufacturing, while providing adequate ancillary fluid structures for mixing and/or routing reaction materials to the process channels without increasing the size and complexity of the microfluidic chip.